APOE ε4-related blood-brain barrier disruption and APOE ε4-independent microstructural abnormalities in white matter hyperintensities.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2026-08-19 eCollection Date: 2026-07-01 DOI:10.1002/dad2.70459

Yuki Oi, Qian Shen, Seraphina K Solders, Charlotte S Rivera, McKenna E Williams, Emilie T Reas

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引用次数: 0

Abstract

Introduction: While the apolipoprotein E (APOE) ε4 allele promotes blood-brain barrier (BBB) permeability and microstructural disruption, its specific contribution to white matter hyperintensity (WMH) pathological heterogeneity remains unknown.

Methods: We measured BBB permeability (K _trans) in 31 and microstructure in 59 cognitively normal older adults with WMHs and normal-appearing white matter (NAWM) using dynamic contrast-enhanced magnetic resonance imaging and restriction spectrum imaging (RSI). Linear mixed-effects models (LMMs) examined differences between WMHs and NAWM by APOE ε4 status.

Results: In APOE ε4 carriers, K _trans was elevated and restricted isotropic diffusion (RI) was reduced within WMHs compared to NAWM. This effect was absent in non-carriers. In contrast, reduced restricted directional diffusion and elevated isotropic free water within WMHs was observed in both genotypes. K _trans did not correlate with brain microstructure.

Discussion: Our data suggest that WMHs comprise both APOE ε4-related and APOE ε4-independent pathological components. These findings implicate neurovascular and non-vascular mechanisms through which APOE ε4 may contribute to WMH pathological heterogeneity.

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APOE ε4相关的血脑屏障破坏和与APOE ε4无关的白质异常。

虽然载脂蛋白E (APOE) ε4等位基因促进血脑屏障（BBB）的通透性和微结构破坏，但其对白质高强度（WMH）病理异质性的具体贡献尚不清楚。方法：采用动态对比增强磁共振成像（dynamic contrast-enhanced magnetic resonance imaging，简称RSI）和限制性波谱成像（restriction spectrum imaging，简称RSI）技术，对59例脑白质（NAWM）和脑白质（WMHs）表现正常的认知正常老年人的脑血脑屏障通透性（K trans）和微观结构进行了测量。线性混合效应模型（lmm）通过APOE ε4状态检验wmh与NAWM之间的差异。结果：在APOE ε4携带者中，与NAWM相比，wmh内K反式升高，限制性各向同性扩散（RI）降低。这种效应在非携带者中不存在。相比之下，在两个基因型中，wmh内限制性定向扩散减少，各向同性自由水增加。K - trans与大脑微观结构无关。讨论：我们的数据表明，wmh既包括APOE ε4相关的病理成分，也包括与APOE ε4无关的病理成分。这些发现暗示APOE ε4可能通过神经血管和非血管机制促进WMH病理异质性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.